Inhibition of CD95-mediated apoptosis through beta 1 integrin in the HSG epithelial cell line |
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Authors: | Dang Howard Dehghan Parastou Lizeth Goodwiler Kai Chen Shuo Zardeneta Gustavo Zhang Bin-Xian Yeh Chih-Ko |
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Institution: |
a Department of Community Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
b Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
c Department of Oral and Maxillofacial Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
d Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
e Department of Geriatric Research, Education and Clinical Center and Research Service, Audie L. Murphy Division, South Texas Veterans Health Care System, Texas
f Department of Dental Diagnostic Science, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA |
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Abstract: | The HSG cell line serves as a model for salivary gland epithelial progenitor cell differentiation. In order for a progenitor cell to differentiate, the cell must maintain viability within its niche. Studies were designed to elucidate the mechanism for integrin-mediated HSG cell survival. HSG cells, grown on Matrigel®, were resistant to CD95-mediated apoptosis. Western blot analysis showed that Matrigel® induced the expression of bcl-2, bcl-xL, p63, and ΔNp63. This induction occurred by as early as 2 hrs and remained for 24 hrs. CD95-mediated apoptosis resistance was dependent, however, upon the expression of the bcl-2 family. Furthermore, Matrigel® induced bcl-2 family expression was dependent on the transactivation of the EGF receptor pathway since PD98059 and AG1478 inhibited Matrigel® induced bcl-2 family expression and caused HSG cells to be sensitive to CD95-mediated apoptosis. Activation of the EGF receptor pathway, by itself, however, was not sufficient to inhibit apoptosis. Blocking antibody showed that bcl-2 family expression was mediated through β1 integrin. These studies show that salivary progenitor epithelial cell survival is integrin dependent and involves the transactivation of the EGF receptor pathway. |
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Keywords: | salivary gland Bcl-2 apoptosis CD95 integrins p63 |
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